V I R O L O G Y More than efficacy revealed by single-cell analysis of antiviral therapeutics

Because many aspects of viral infection dynamics and inhibition are governed by stochastic processes, single-cell analysis should provide more information than approaches using population averaging. We have developed a microfluidic device composed of ~6000 wells, with each well containing a microstructure to capture single, infected cells replicating an enterovirus expressing a fluorescent reporter protein. We have used this system to characterize enterovirus inhibitors with distinct mechanisms of action. Single-cell analysis reveals that each class of inhibitor interferes with the viral infection cycle in a manner that can be distinguished by principal component analysis. Single-cell analysis of antiviral candidates not only reveals efficacy but also facilitates clustering of drugs with the same mechanism of action and provides some indication of the ease with which resistance will develop

Mechanism for Selective Binding of Aromatic Compounds on Oxygen-Rich Graphene Nanosheets Based on Molecule Size/Polarity Matching

Selective binding of organic compounds is the cornerstone of many important industrial and pharmaceutical applications. Here, we achieved highly selective binding of aromatic compounds in aqueous solution and gas phase by oxygen-enriched graphene oxide (GO) nanosheets via a previously unknown mechanism based on size matching and polarity matching. Oxygen-containing functional groups (predominately epoxies and hydroxyls) on the nongraphitized aliphatic carbons of the basal plane of GO formed highly polar regions that encompass graphitic regions slightly larger than the benzene ring. This facilitated size match–based interactions between small apolar compounds and the isolated aromatic region of GO, resulting in high binding selectivity relative to larger apolar compounds. The interactions between the functional group(s) of polar aromatics and the epoxy/hydroxyl groups around the isolated aromatic region of GO enhanced binding selectivity relative to similar-sized apolar aromatics. These findings provide opportunities for precision separations and molecular recognition enabled by size/polarity match–based selectivity

An approximate renormalization-group transformation for Hamiltonian systems with three degrees of freedom

We construct an approximate renormalization transformation that combines Kolmogorov-Arnold-Moser (KAM)and renormalization-group techniques, to analyze instabilities in Hamiltonian systems with three degrees of freedom. This scheme is implemented both for isoenergetically nondegenerate and for degenerate Hamiltonians. For the spiral mean frequency vector, we find numerically that the iterations of the transformation on nondegenerate Hamiltonians tend to degenerate ones on the critical surface. As a consequence, isoenergetically degenerate and nondegenerate Hamiltonians belong to the same universality class, and thus the corresponding critical invariant tori have the same type of scaling properties. We numerically investigate the structure of the attracting set on the critical surface and find that it is a strange nonchaotic attractor. We compute exponents that characterize its universality class.Comment: 10 pages typeset using REVTeX, 7 PS figure

Total harmonic distortion based method for linearity assessment in electrochemical systems in the context of EIS

Electrochemical Impedance Spectroscopy (EIS) is a widely used electrochemical measurement technique that has been used in a great spectrum of fields since it allows deconvolving the individual physic- chemical processes that take place in a given system. Ohm s generalized law, and thus the impedance concept, are only valid if 4 conditions are fulfilled: causality, finiteness, stationarity and linearity. In the case that any of these conditions is not achieved, the obtained impedance spectra will present distortions that may lead to biased or even erroneous results and conclusions. For this reason it is crucial to verify if the 4 conditions are fulfilled, before accepting the results extracted from impedance spectra. In this work, a linearity assessment quantitative method based in the total harmonic distortion (THD) parameter is presented and verified experimentally. The experimental validation of the implemented method showed that the implemented method is able to assess quantitatively the linearity of the system. In addition, it is also able to determine the threshold frequency above which the system will not present significant nonlinear effects even for large perturbation amplitudes. It was observed that the THD method is more sensitive to nonlinear effects than the spectra themselves.The authors are very grateful to the Generalitat Valenciana for its economic support in form of Vali+d grant (Ref: ACIF-2013-268).Giner Sanz, JJ.; Ortega Navarro, EM.; Pérez-Herranz, V. (2015). Total harmonic distortion based method for linearity assessment in electrochemical systems in the context of EIS. Electrochimica Acta. 186:598-612. https://doi.org/10.1016/j.electacta.2015.10.152S59861218

Equation of state and phonon frequency calculations of diamond at high pressures

The pressure-volume relationship and the zone-center optical phonon frequency of cubic diamond at pressures up to 600 GPa have been calculated based on Density Functional Theory within the Local Density Approximation and the Generalized Gradient Approximation. Three different approaches, viz. a pseudopotential method applied in the basis of plane waves, an all-electron method relying on Augmented Plane Waves plus Local Orbitals, and an intermediate approach implemented in the basis of Projector Augmented Waves have been used. All these methods and approximations yield consistent results for the pressure derivative of the bulk modulus and the volume dependence of the mode Grueneisen parameter of diamond. The results are at variance with recent precise measurements up to 140 GPa. Possible implications for the experimental pressure determination based on the ruby luminescence method are discussed.Comment: 10 pages, 6 figure

Mass measurements of neutron-deficient Y, Zr, and Nb isotopes and their impact on rp and νp nucleosynthesis processes

© 2018 The Authors. Published by Elsevier B.V. This manuscript is made available under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence (CC BY-NC-ND 4.0). For further details please see: https://creativecommons.org/licenses/by-nc-nd/4.0/Using isochronous mass spectrometry at the experimental storage ring CSRe in Lanzhou, the masses of 82Zr and 84Nb were measured for the first time with an uncertainty of ∼10 keV, and the masses of 79Y, 81Zr, and 83Nb were re-determined with a higher precision. The latter are significantly less bound than their literature values. Our new and accurate masses remove the irregularities of the mass surface in this region of the nuclear chart. Our results do not support the predicted island of pronounced low α separation energies for neutron-deficient Mo and Tc isotopes, making the formation of Zr–Nb cycle in the rp-process unlikely. The new proton separation energy of 83Nb was determined to be 490(400) keV smaller than that in the Atomic Mass Evaluation 2012. This partly removes the overproduction of the p-nucleus 84Sr relative to the neutron-deficient molybdenum isotopes in the previous νp-process simulations.Peer reviewe

Structure and Dynamics of Liquid Iron under Earth's Core Conditions

First-principles molecular dynamics simulations based on density-functional theory and the projector augmented wave (PAW) technique have been used to study the structural and dynamical properties of liquid iron under Earth's core conditions. As evidence for the accuracy of the techniques, we present PAW results for a range of solid-state properties of low- and high-pressure iron, and compare them with experimental values and the results of other first-principles calculations. In the liquid-state simulations, we address particular effort to the study of finite-size effects, Brillouin-zone sampling and other sources of technical error. Results for the radial distribution function, the diffusion coefficient and the shear viscosity are presented for a wide range of thermodynamic states relevant to the Earth's core. Throughout this range, liquid iron is a close-packed simple liquid with a diffusion coefficient and viscosity similar to those of typical simple liquids under ambient conditions.Comment: 13 pages, 8 figure

Single-Cell Virology: On-Chip Investigation of Viral Infection Dynamics

We have developed a high-throughput, microfluidics-based platform to perform kinetic analysis of viral infections in individual cells. We have analyzed thousands of individual poliovirus infections while varying experimental parameters, including multiplicity of infection, cell cycle, viral genotype, and presence of a drug. We make several unexpected observations masked by population-based experiments: (1) viral and cellular factors contribute uniquely and independently to viral infection kinetics; (2) cellular factors cause wide variation in replication start times; and (3) infections frequently begin later and replication occurs faster than predicted by population measurements. We show that mutational load impairs interaction of the viral population with the host, delaying replication start times and explaining the attenuated phenotype of a mutator virus. We show that an antiviral drug can selectively extinguish the most-fit members of the viral population. Single-cell virology facilitates discovery and characterization of virulence determinants and elucidation of mechanisms of drug action eluded by population methods. Guo et al. use a microfluidics device installed on a fluorescence microscope to monitor the kinetics of viral infection in single cells. Between-cell variation in outcomes of infection exists at all phases of the life cycle. Cellular gene expression governs the eclipse phase; viral genetics govern replication rate and yield

Magnetic Fields in the Milky Way

This chapter presents a review of observational studies to determine the magnetic field in the Milky Way, both in the disk and in the halo, focused on recent developments and on magnetic fields in the diffuse interstellar medium. I discuss some terminology which is confusingly or inconsistently used and try to summarize current status of our knowledge on magnetic field configurations and strengths in the Milky Way. Although many open questions still exist, more and more conclusions can be drawn on the large-scale and small-scale components of the Galactic magnetic field. The chapter is concluded with a brief outlook to observational projects in the near future.Comment: 22 pages, 5 figures, to appear in "Magnetic Fields in Diffuse Media", eds. E.M. de Gouveia Dal Pino and A. Lazaria